Mass-dependent signaling between G protein coupled receptors

Cell Signal. 2006 Apr;18(4):564-76. doi: 10.1016/j.cellsig.2005.06.011. Epub 2005 Aug 24.


The present study provides evidence that G protein coupled receptor (GPCR) signaling pathways participate in an interactive signaling network governed by the principles of mass action. Using an inducible thromboxane A2 receptor (TPR)/platelet activating factor receptor (PAFR) co-expressing cell model, TPR or PAFR expression was independently up-regulated. Immunostaining and radioligand binding experiments demonstrated that this receptor up-regulation resulted in increased GPCR:G protein mass ratios. This increase in mass ratio impacted both TPR and PAFR ligand affinity. Specifically, up-regulating TPR expression not only decreased TPR ligand affinity, but also decreased the ligand affinity of PAFRs. A similar effect on ligand affinities was observed when PAFRs were up-regulated. In addition, increasing the GPCR:G protein mass ratio for TPRs led to desensitization of the calcium mobilization response to PAFR activation, and increasing PAFR mass desensitized the TPR-mediated calcium response. Finally, it was observed that an increased TPR:G protein mass ratio was associated with a shift in the TPR signaling response, and revealed an additional TPR signaling pathway through G(S). Collectively, these results describe a novel mechanism, i.e., mass-dependent GPCR signaling, by which cells can modulate their GPCR signaling pathways and signaling priorities.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Azepines / pharmacology
  • Blood Platelets / drug effects
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Humans
  • Ligands
  • Platelet Membrane Glycoproteins / antagonists & inhibitors
  • Platelet Membrane Glycoproteins / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Thromboxane A2, Prostaglandin H2 / agonists
  • Receptors, Thromboxane A2, Prostaglandin H2 / antagonists & inhibitors
  • Receptors, Thromboxane A2, Prostaglandin H2 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Time Factors
  • Triazoles / pharmacology
  • Up-Regulation


  • Azepines
  • Ligands
  • Platelet Membrane Glycoproteins
  • Receptors, G-Protein-Coupled
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Triazoles
  • platelet activating factor receptor
  • WEB 2086
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Calcium